THE ROLE OF HYDRATION IN THE HYDROLYSIS OF PYROPHOSPHATE - A MONTE-CARLO SIMULATION WITH POLARIZABLE-TYPE INTERACTION POTENTIALS

The exchange of energy in biochemical reactions involves, in a majorit y of cases, the hydrolysis of phosphoanhydrides (P-O-P). This discover y has lead to a long discussion about the origin of the high energy of such bonds, and to a proposal that hydration plays a major role in th e energetics of the hydrolysis. This idea was supported by recent ab i nitio quantum mechanical calculations (Saint-Martin et al. (1991) Bioc him. Biophys. Acta 1080, 205-214) that predicted the hydrolysis of pyr ophosphate is exothermic in the gas phase. This exothermicity can acco unt for only a half of the total energy release that one measures in a queous solutions. Here we address the problem of hydration of the reac tants and products of the pyrophosphate hydrolysis by means of Monte C arlo simulations, employing polarizable potentials whose parameters ar e fitted to energy surfaces computed at the SCF/6-31G(*) level of the theory. The present results show that the hydration enthalpies of the reactants and products contribute significantly to the total energy o utput of the pyrophosphate hydrolysis. The study predicts that both, t he orthophosphate and the pyrophosphate, have hydration spheres with t he water molecules acting as proton accepters in the P-OH...O(water) h ydrogen bonds. These water molecules weakly repel the water molecules in the further hydration spheres. The perturbation of the structure of the solvent caused by the presence of the solute molecules is short r anged: after ca. 5 Angstrom from the P atoms, the energy and the struc ture of water correspond to bulk water. Due mainly to nonadditive effe cts, the molecular structure of the hydrated pyrophosphate is quite di fferent from two fused structures of the hydrated orthophosphates. The hydration sphere of pyrophosphate is very loose and has a limited eff ect on the water network, whereas for orthophosphate it has a well dev eloped shell structure. Hence, upon hydration there will be both a gai n in hydration enthalpy and a gain in entropy because of distortion of the water molecular network.